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Student 2: C+
Susak
ENG3010
July 5, 2015
Literature Review
Introduction
Over 6 million people in the U.S. are affected by blindness and visual imparities,
out of the 6 million, 20% cannot currently be cured (National Federation of the Blind).
Within all the research done, it has been accepted that once the functioning eye
disconnects from its nerves, they cannot be fully reconnected (An End to Blindness).
Once the retina has disconnected from the optic nerve, eyes will begin to degenerate due
to limited stimulation (Curing Blindness: Vision Quest). For patients 65 years or older,
once degeneration occurs, it can only be slowed down, but not cured. Degeneration is
caused by disconnects between rods/cones and the nerves in the eye.
Stem cells are undifferentiated somatic cells found in cord cells and embryos.
They serve as cells, which haven’t been specialized to a specific part of the body, so in
turn they can become any type of cell. In the human body they serve as an automatic
maintenance to repair body functions (Bauman). Under controlled conditions, stem cells
can be manipulated with proteins to behave in specific ways. Stem cells also adapt the
behavior of cells around them to fit into their location (Bauman). If we can get stem cells
to behave as we want within the eye we have the ability to create regeneration of vision.
During development, stem cells are controlled by they embryo in order to form in the
correct order so the goal would be to monitor that behavior and figuring out how to apply
it to the eye. While trying to gain a better understanding of how this works in embryos,
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the question is, how can we control these stem cells in order to regenerate lost visual
tissue in the eye?
Retinal Degeneration
Retinal degeneration falls into 3 major categories; rod-degeneration, rod/conedegeneration, and debris based degeneration (Jayakody, Cordero, Ali, Pearson). Although
the different types vary in intensity and form, they are all majorly caused by old age.
During this time, the photoreceptor of the eye (rods and cones), which serves to convert
light to neurons, slowly begin to disconnect from the retina, loosing their connection
from the nerves (Jayakody et. al). When the connection is lost, the impulses of light
cannot travel to the occipital lobe where they are converted to what we see (Jayakody et.
al).
The degeneration is also seen in the embryo stages. This is brought on by genetic
mutations or trauma to the baby during fetal stages. Any sort of genetic mutation is
caused through homeobox genes, in turn by understanding how those genes cause
malformations, we can better understand how to reverse it (Hill, Favor, Hogan, Ton,
Saundars, Hanson, pg.522). In cases like this, two major scenarios take place. One form
of the degeneration can be that the eyes simply don’t form, although the retinal nerve will
still be in place, the retina will have not formed. Parts of the eye will be in their correct
places, but there will be a loss of connection from the photoreceptors and the nerve,
similar to the degeneration due to old age.
Current Work In Stem Cells For Retina Regeneration
In research done, researchers have seen successful results when using stem cells
based procedures. When working with chick embryos, researchers implanted genetically
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formed replacements into the degenerated eye and saw results of regained vision
(Coulombre, Coulombre). They replaced the neural retina of the chicks at different times
post-degeneration and they saw that when replaced immediately, the vision was
corrected, but anything replaced after a 4-day period would not form because there was a
loss of stem cells in order to reform attachments in the nerves (Coulombre et. al). Many
methods were tested in response to the differences caused by the time period of the
implantation. One alternative method tested was doing it in steps, so removing the old
eye one day and implanting the new eye the next day, but nothing yielded results like
implanting everything in one day (Coulombre et. al).
Acting in a more straightforward pattern, researchers have also attempted to plant
stem cells directly into the eye to follow the path it takes to reform the eye (Tropepe,
Coles, Chiasson, Horsford, Elia, McInnes, Van Der Kooy). When doing this they saw
that the stem cells would reform, but sight would not be restored because the stem cells,
although adapting to the cells around them, would not behave as normal retinal cells
(Tropepe et. al). This showed potential in the path of understanding how we can reform
damaged cells, but function remains the issue.
Farrar, Ward, Palfi, Chadderton, and Kenna believe that by understanding the
modular abilities within the optical nerve, they can gain control over functions of the eye
as well as understand how to reverse vision loss done through optic nerve damage. When
referring to modular strengths, it refers to the singular separations of the optic nerve
attaching to each rod or cone (Farrar et. al).
Adler talks extensively about the use of stem cells in both cloning and attachment
of an eye for repair of vision loss. By using stem cells to clone an alternative eye, you can
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create the identical eye without any damage (Adler) and implant it using knowledge on
optic modules (Farrar et. al)
Stem Cell Work In Other Fields
Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) studies
In patients with Parkinson’s disease, they face degeneration in a specific strain of
neural cells. Researchers feared that replicating the behavior of these cells would be
difficult because not only are the details of the cells still unknown, but they are adult cells
which meant getting stem cells to behave as adult cells could take time (Lindvall, Kokaia,
Serrano). When implanted into the degenerative part of the brain, the potential of stem
cells was seen in that they immediately began to replace the dead neural cells. Although
this process was not enough to fully eliminate degeneration, it slowed down the
progression of the disease enough for us to monitor how the cells behave in highly
differentiated parts of the body (Lindvall et. al). Understanding how these stem cells
behave in the nerves of the body is vital in the possible application to the retina. Because
the retina is such a sensitive part of the body, by applying the studies to other parts of the
body first helps us get a better understanding of stem cells before direct application to the
retina.
With ALS and MS being central nervous system diseases, we see that stem cells
are not limited in application when discussing nerves, which is one of the overarching
issues in vision loss. This allows for anticipation of nerve recovery in the eye. Comparing
this to the previous study done by Coulomre and Coulombre, there is overlap in the
application of stem cells in order to regain nerve function. Through out rat based studies
there has been visible improvements made in damaged nerve cells throughout the body
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(Kniery, DeHart, Brown, Salgar). If researchers can combine the strength of stem cells
within the eye (Coulombre et. al) with a better understanding of modules from the optic
nerve (Farrar et. al), it will create a better overall understanding of the eye in order to
expand the methods of research on the retina.
Cancer Cell Studies
Cancerous stem cells allow us to see the pit falls of stem cell use in the human
body. In studied tumors, a similar characteristic seen surrounding the mass is an
abundance of stem cells that continue to divide and grow on the tumor. When studied
these cells show a lack of control via the body and DNA (Jordan, Guzman, Noble). The
cells behave individual of the body. By studying these stem cells, researchers are able to
produce their counterparts, stem cells engineered to control cancer cells by applying
control proteins to the cells to inhibit growth (Jordan et. al). Not only does this treatment
allow us to control cancer cells, but also it allows researchers to cater their control over
cells to get them to behave in the way they want through using proteins and gene markers
on cells, which can be applied to retinal cells (Seneviratne, Ma, Tan, Kwon, Muhammad,
Melham, Defrances, Zarnagar). When applying proteins and gene markers on cells, you
are deciding which kinds of proteins the cells will produce and it will behave in the way
the proteins dictate it too.
The gene markers on cells can also be used to reverse malformations and
degeneration in cancer cells (Seneviratne et. al). Using this feature of stem cells in the
eye gives more freedom for experimentation. The next step for studies would be to
understand how gene markers work on retinal cells.
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Conclusion; Combining Our Knowledge
Central nervous system stem cells therapies have showed that stem cell
manipulation is possible in order to reverse years of damage. We see that stem cells aptly
behave in accordance with their surrounding not matter how specialized. In primarily
neural regions of the body, each individual cells placement in not as direct because the
connections forming are from all sides. Due to the broad placement of cells within the
eye we see that when stem cells are used directly in the eye, they will form all the correct
parts of the eye, but there in no control over their directed function so they wont do the
correct task.
Cancer cell have proven the capability of designing very specific cells made to
work in their own ways inside the body. By using this in stem cells, we have the
capabilities to create replicas of the eye outside of the human body through genetic
modification. Through research, we can create a better understanding of how the retina
works to capture messages and convey them to the optic nerve through single modules.
By combining the knowledge we have on stem cells and the eyes, we have the power to
ask the question; can researchers use the power of stem cells along with gene markers
and proteins to create reversal of blindness and visual impairments?
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Works Cited
Kniery, Kevin, et al. "Stem cell and novel biologic therapies to enhance functional
recovery in vascular composite allotransplantation (TRAN1P. 922)." The Journal of
Immunology 194.1 Supplement (2015): 140-4.
Seneviratne, Danushka, et al. "Genomic instability causes HGF gene activation in colon
cancer cells, promoting their resistance to necroptosis." Gastroenterology 148.1 (2015):
181-191.
Farrar, Gwyneth Jane, et al. "Gene Therapy for Dominantly Inherited Retinal
Degeneration." Gene-and Cell-Based Treatment Strategies for the Eye. Springer Berlin
Heidelberg, 2015. 43-60.
Baumann, Kim. "Stem cells: Human primordial germ cells in a dish." Nature Reviews
Molecular Cell Biology (2015).
Lindvall, Olle, Zaal Kokaia, and Alberto Martinez-Serrano. "Stem Cell Therapy for
Human Neurodegenerative Disorders–how to Make It Work." Nat Med Nature Medicine
10.7 (2004): n. pag. Web.
Tropepe, V. "Retinal Stem Cells in the Adult Mammalian Eye." Science 287.5460
(2000): 2032-036. Web.
Jayakody, Sujatha A., Anai Gonzalez-Cordero, Robin R. Ali, and Rachael A. Pearson.
"Cellular Strategies for Retinal Repair by Photoreceptor Replacement." Progress in
Retinal and Eye Research 46 (2015): 31-66. Web.
"Treating Blindness and Vision Loss - Restoring Eyesight - AARP." AARP. N.p., n.d.
Web. 16 July 2015. <http://www.aarp.org/health/conditions-treatments/info2015/treating-blindness-vision-loss.html>.
Ton, Carl CT, Grady F. Saunders, and Nicholas D. Hastie. "Mouse small eye results from
mutations in a paired-like homeobox-containing gene." Nature 354 (1991): 19.
Adler, Ruben. "Curing blindness with stem cells: hope, reality, and challenges." Recent
Advances in Retinal Degeneration. Springer New York, 2008. 3-20.
Jordan, Craig T., Monica L. Guzman, and Mark Noble. "Cancer Stem Cells." New
England Journal Of Medicine (2006): n. pag. Web. 16 July 2015.
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Invention Portfolio
Revised Research Questions
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Can blindness be cured with the use of stem cells?
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Can a cloned eye be implanted into the eye?
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How far can we go when using stem cells in the eye?
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Ethics of cloning?
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Can we use the same techniques of stem cells on other parts of the body on
the eyes?
Launch Texts
"Adult stem cell advances." Ethics & Medicine: an international journal of bioethics 22.2
(2006): 124. Academic OneFile. Web. 24 June 2015.
Horton, Sarah J., and Brian J.P. Huntly. “Recent Advances in Acute Myeloid Leukemia
Stem Cell Biology.” Haematologica 97.7 (2012): 966–974. PMC. Web. 24 June 2015.
Viczian, Andrea S. “Advances in Retinal Stem Cell Biology.” Journal of Ophthalmic &
Vision Research 8.2 (2013): 147–159. Print.
Graphic Organizer
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Shitty Rough Draft
Both my articles are two versions of journals based around stem cell
research. One of them is an academic journal and the other is a research journal,
they both focus around the progression of stem cell research and the future
discoveries that can be made. Just one person does more generally not write these
journals. The academic journal uses information from other sources to tie it
together and present preexisting information. Research articles are doing active
research and making new discoveries about planned topic.
My research article focuses on the progression of stem cells in retinal
transplants. They are trying to figure out how using stem cells can regenerate
eyesight in patients who have had damage to their retinas. Their initial goal is to see
how they can get stem cells to mimic the behavior of retinal cells and they are trying
to document the steps it takes for the cells to get to the same state as the other cells.
The process begins by trying to understand what differentiates a retinal cell
from others. They do this by looking at all markers and confinements on the genes
in retinal cells. The goal is to replicate all actions of proteins from a retinal cell to
stem cells. Once this process is achieved, they begin actually applying the factors
onto the cells. This process shows to be tricky because not all of the proteins will
attach to the genes in the way you intend them too, so as result they include a very
detailed map showing what processes worked as opposed to others. Once the cells
have been molded into replicas of the retinal cells, they allow the cells to grow, both
to see how they behave as well as to understand if they will take on similar activities
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to the real retinal cells. When they complete their research, they find that there are
ways to replicate the activities of retinal cells through stem cells.
In the academic journal I chose, they are laying out all the capabilities of stem
cells. They connect many articles to show the strength of stem sells and how they
can help with progression of cancer treatments, dementia, and genetic diseases. The
bulk of the content is based around cancer. Many studies have been done to show
that through using stem cells, you can create a cell meant to attack specific
cancerous cells. This is something the body naturally attempts to do but the cells are
to weak to act on tumors. By creating these specific attack cells, you are able to gain
control over growing tumor cells.
Another cancer research in this journal shows that by creating replicas of
tumors outside of the body, we can track how they progress and change through
different stages in order to create the best plan of attack for when this mass is still
inside the body. This is something that can be done very broadly for all different
types of tumors and cancers. By creating more forward movement in this research
we see that cancer discoveries are at our fingertips, but is just a matter of doing the
research to progress.